![](//www.4rfv.com/4rfv_news_images/scripps_scripts/OGIKCYWBM0JL_0.jpg)
Scripps Research chemists develop new method for making gamma chiral centers on simple carboxylic acids C-H activation-based method should speed drug molecule design and diversification.
May 17, 2024
LA JOLLA, CA Scripps Research chemists have accomplished a long elusive feat in synthetic chemistry: the invention of a broadly useful method for constructing gamma chiral centers on simple starting compounds called carboxylic acids. The method, published on May 16, 2024 in Science, significantly extends the ability of chemists to build and modify complex pharmaceutical molecules and other valuable chemical products.
The term chiral refers to a type of asymmetry that allows some chemical compounds to exist in left-handed and right-handed forms. Often, only one of these forms has the desired biochemical activity, but for synthetic chemists, stereoselective reactions those that yield just the desired form are almost always challenging.
The new method enables what had been impossible except in narrow cases: creating a center of chiral asymmetry at a hard-to-reach position called the gamma position on a cyclic carboxylic acid.
This approach offers unprecedented and relatively easy access to a broad set of chiral carbocycles that are privileged structures for pharma industry drug discovery programs, says study senior author Jin-Quan Yu, PhD, Frank and Bertha Hupp Professor of Chemistry and Bristol Myers Squibb Endowed Chair in Chemistry at Scripps Research.
The co-first authors were Tao Zhang, PhD, and Zi-Yu Zhang, PhD, both postdoctoral research associates in the Yu lab.
A potentially valuable but elusive method
The development of small molecule pharmaceuticals or other chemical products typically involves the construction of many hundreds or thousands of compounds, each representing a variation on a central structural theme. Once these libraries of compounds are constructed, they are methodically tested for the desired biological or chemical activity; in this way, developers can zero in on the best compound for further refinement. Naturally, in constructing these libraries and in making more refined variants, chemists would like to have easy and versatile techniques for building and modifying molecules. But while their tools have greatly improved over the years, some types of molecular transformation have remained essentially undoable, despite the obvious value they would have. Gamma chiral center construction using readily available carboxylic acids has been one of these, defying the efforts of prominent synthetic chemistry labs.
The Yu lab's success hinged on the development of special ligand molecules containing both oxazoline and pyridone structural elements. Ligand molecules help bring the reaction catalyst to the right spot on the initial compound. In this case, they fasten to one point on the starting carboxylic acid which contains a ring of mostly carbon atoms and direct a bond-breaking palladium atom to the distant gamma position on the other side of the ring. The effect is to remove a hydrogen atom from the backbone carbon atom at the targeted spot, allowing a new cluster of atoms to bond to the carbon thus adding complexity to the molecule in a precise way.
This type of reaction is called a C-H activation, and over the past decade, Yu and his team have reported similar C-H activation methods for constructing chiral centers at alpha and beta positions on carboxylic acids.
The chemists demonstrated the power and versatility of their new method by using it to make gamma chiral centers on a wide variety of relatively simple carboxylic acid starting compounds containing rings of from five to eight carbon atoms. In one case, they achieved a single-step synthesis of a chiral version of a cancer drug molecule called an HDAC inhibitor whose standard, patented synthesis method requires 10 steps and a costly separation to obtain pure samples of the left-handed or right-handed form.
The team also used the new technique to add complexity to existing drug molecules, including the steroid hormone pregnenolone.
Finally, the chemists showed they could use their new approach sequentially on a starting molecule to construct three chiral centers including a very challenging delta chiral center.
The Yu lab is now working to extend the new approach so it can be used for making other types of chiral molecules.
Enantioselective Remote Methylene C H (Hetero)Arylation of Cycloalkane Carboxylic Acids was co-authored by Tao Zhang, Zi-Yu Zhang, Guowei Kang, Tao Sheng, Jie-Lun Yan, Yuan-Bin Yang, Yuxin Ouyang and Jin-Quan Yu, all of Scripps Research.
Support for the research was provided by the National Institutes of Health (2R01GM084019).
Chemistry Yu, Jin-Quan
North America Stories
26/07/2024
by Ianeta Le'i
I honestly don't remember the first time I met Bryson Ch...
26/07/2024
(L-R) Louise (Karen Gillan) and Antonina (Margaret Sophie Stein) strike up an un...
26/07/2024
Orders1 of $5.2 billion; book-to-bill of 1.0x
Revenue of $5.3 billion, up 13%
...
26/07/2024
(Editor's note: TVTech reached out to several station groups to determine the impact of the CrowdStrike outage on operations. Many, including NextStar Media...
26/07/2024
NEWPORT BEACH, Calif. Bitcentral has integrated Pixalate's ad fraud protection, privacy and compliance analytics solution Post-Bid Analytics and Reporting i...
26/07/2024
Aldous Huxley's classic novel Brave New World is a science fiction thriller set in a murky future with a highly ordered society. While Huxley and other sc...
26/07/2024
Hollyland Adds Pyro 7 All-in-one Video Monitor, TX and RX to Pyro Series
Brie Clayton July 26, 2024
0 Comments
Seven-inch 2.4/5GHz wireless monitor wi...
26/07/2024
Geddy Lee Asks Are Bass Players Human Too? Graded Using DaVinci Resolve Studio
Brie Clayton July 26, 2024
0 Comments
Blackmagic today announced that t...
26/07/2024
Another reminder of the popularity of ad-supported connected TV comes in a survey by Premion and Advertiser Perceptions which found that 61% of the marketers th...
26/07/2024
Nielsen's Gracenote unit said it is selling its metadata about the content of television shows and movies for use in targeting connected-TV advertising camp...
26/07/2024
CBS premieres 13 Days in Ferguson, a special about the aftermath of a police shooting of a young Black man in 2014, on Friday, August 9. The special features Ce...
26/07/2024
Disney and Warner Bros. Discovery announced the launch of their long-awaited premium streaming bundle for the United States. For $16.99 per month, subscribers w...
26/07/2024
Florida-based Video Village Miami provides on-set video assist for local commercials and music videos. Frank Collins established the outfit in 2019 after a 20-y...
26/07/2024
QuickLink, the leading global provider of multi-camera video productions and remote contribution solutions, will present QuickLink StudioPro at IBC 2024 (Stand ...
26/07/2024
Relo Metrics (formerly GumGum Sports), the leading AI-powered sponsorship analytics platform for real-time data decisions, today launched an industry-leading in...
26/07/2024
Anton/Bauer, a leading provider of mobile power systems for the film and television industry, has announced the launch of the VCLX LI 1600. The latest evolution...
26/07/2024
Bitcentral, the leading provider of professional media solutions for broadcast and digital video, today announces that it has integrated Pixalate, the ad fraud ...
26/07/2024
Cobalt Iron Inc., a leading provider of SaaS-based enterprise data protection, today announced that Secure Automated Backup with Compass , a cloud backup-as-a-s...
26/07/2024
VisualOn IBC2024 Exhibitor Preview
Sept. 13-16
Amsterdam
Stand 5.A52
As video streaming consumption surges, service providers face significant challenges wi...
26/07/2024
Quanteec
IBC2024 Exhibitor Preview
Sept. 13-16
RAI Amsterdam
Stand 1.A05
Quanteec, a global provider of video delivery technology for broadcasters, will s...
26/07/2024
Witbe
IBC2024 Exhibitor Preview
Sept. 13-16
Amsterdam
Stand 5.F84
At IBC2024, Witbe will showcase the power of its automated testing and proactive monitori...
26/07/2024
WASHINGTON, D.C. The Federal Communications Commission has announced the launch of its new Mobile Speed Test app. The new app features an enhanced user interfac...
26/07/2024
LONDON In a notable landmark for the use of cloud-based services at the Olympics, Alibaba Cloud and Olympic Broadcasting Services (OBS), has today announced the...
26/07/2024
NEW YORK As part of a $2.5 billion media rights deal with the NBA announced on July 24, NBCUniversal and the NBA have also announced an 11-year agreement for ri...
26/07/2024
BEAVERTON, Ore. Versatile Video Coding (VVC) promises to play a pivotal role in driving advancements in video compression technology, with organizations across ...
26/07/2024
COLUMBUS, Ohio The political news channel PurpleTV has expanded it reach with news that it has launched on Channel 25.1 in Columbus, Ohio on TV Station WXOH, wh...
26/07/2024
NEW YORK As part of a push into the contextual advertising business, Nielsen's Gracenote has announced that it is developing new contextual categories to gi...
26/07/2024
Puget Systems Returns to SIGGRAPH 2024 to Demonstrate its On-Premises Generative...
26/07/2024
Dreamtek Delivers Innovative A/V, Live Production and Post Workflows with Blackm...
26/07/2024
Dejero to bring even smarter' mobile internet connectivity solutions to IBC...
26/07/2024
The 2024 Paris Olympic Games are about to begin, and Capitol Broadcasting is rea...
26/07/2024
Berklee Alumni Nominated for 2024 Emmy Awards Twenty-one Berklee alumni received Emmy nominations this year for music composition, sound mixing, and sound editi...
26/07/2024
Jennifer Lyons, president and general manager of WBBM Chicago, is moving into a ...
26/07/2024
Kennan Oliphant has been named VP of news and station manager at WWJ Detroit. He will report to Jennifer Lyons, who has added a regional GM role that gives her ...
26/07/2024
Charlie Hustle & The Matter of Pete Rose, a four-part docuseries, debuts on HBO and Max July 24. The series details the life of the baseball superstar, includin...
26/07/2024
The 2024 Paris Olympic Games present a unique and exciting opportunity for local...
26/07/2024
Paris 2024: V varo Providing Live Media Transport Services for Leading Internati...
26/07/2024
Paris 2024: BBC Sport on Its Remote Production Workflow for the Summer Games By Heather McLean, SVG Europe
Friday, July 26, 2024 - 7:31 am
Print This Story...
26/07/2024
Paris 2024: BBC Sport Unveils the Olympic Storytelling and Breathtaking Scenery ...
26/07/2024
Paris 2024: Taking a Step Forwards with BBC Sport's Olympic Studio Combining...
26/07/2024
Paris 2024: Warner Bros. Discovery Sports Europe Provides a First Look at Its Ol...
26/07/2024
Live From Paris 2024: NBC Olympics Set for Historic Opening Ceremony Unilateral coverage builds on impressive OBS production as NBC dives deep into Team USA cov...
26/07/2024
Live From Paris 2024: SVG's Onsite Editorial Team Breaks Down Opening Ceremo...
26/07/2024
Back to All News
Suspense Thriller The Frog' Set to Give Viewers the Chills on August 23Play Video
Play Video
Entertainment
26 July 2024
GlobalSouth K...
26/07/2024
Back to All News
Can't Get Enough of K-Variety? New Unscripted Series Debut...
26/07/2024
Back to All News
Netflix Announces Salvador, a New Series Created by Aitor Gabi...
26/07/2024
Timing matters: Scripps Research study shows ways to improve health alerts Wearable health sensors are a powerful tool in disease detection and in stemming the ...
25/07/2024
SWANSEA, U.K. QuickLink will show its QuickLink StudioPro 4K video production platform at IBC 2024, Sept. 13-16, at the RAI Amsterdam Convention Center....
25/07/2024
STAMFORD, Conn. and DENVER, Colo. NBC Sports has announced that it will be using Comcast Technology Solutions (CTS) to provide multiscreen video management and ...
25/07/2024
LONDON Pixalate, a fraud protection, privacy, and compliance analytics platform for connected TV (CTV) and mobile advertising, has released a new report highlig...